First-Generation Bioresorbable Vascular Scaffolds

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL. 69, NO. 25, 2017

ª 2017 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

ISSN 0735-1097/$36.00

PUBLISHED BY ELSEVIER

http://dx.doi.org/10.1016/j.jacc.2017.04.012

EDITORIAL COMMENT

First-Generation Bioresorbable Vascular Scaffolds Disappearing Stents or Disappearing Evidence?* Sripal Bangalore, MD, MHA,a Elazer R. Edelman, MD, PHD,b Deepak L. Bhatt, MD, MPHc

S

ignificant progress in percutaneous coronary

vasomotion (2), with a consequent potential greater

intervention (PCI) technology over the last 3

decrease in angina as a result of “uncaging” of the

decades has provided contemporary drug-

artery; and mitigation of stent-related adverse events

eluting stents (DES) that have a low risk of restenosis

and reduction in need for extended duration dual

and a very low risk of stent thrombosis (1). In the

antiplatelet therapy (DAPT). As such, this therapy

small proportion of patients who develop in-stent

has been heralded as the next paradigm shift in PCI

restenosis, the risk of recurrent in-stent restenosis is

technology, and several hospitals have issued press

high, whether treated with a second-generation DES

releases touting the benefits of the BVS on the basis

or a drug-coated balloon, and the location of the

of these theoretical benefits. Although many bio-

stented segment may preclude coronary artery

erodible implants are currently in development, in

bypass graft placement. As such, bioresorbable

2016, the Absorb scaffold (Abbott Vascular, Santa

vascular scaffolds (BVS) hold promise that the options

Clara, California), a 150-m m-thick, first-generation

for

artery

scaffold, became the first to receive Food and Drug

bypass graft surgery, will be preserved after the scaf-

Administration approval. To justify its use, the

folds disappear. Several other theoretical advantages

scaffold should be proven at least noninferior to the

include: expansive remodeling and return of coronary

current best available DES in the resorption phase

*Editorials published in the Journal of the American College of Cardiology

Research Institute (St. Jude Medical, now Abbott), Mayo Clinic, and

reflect the views of the authors and do not necessarily represent the

Population Health Research Institute; and has received honoraria from

views of JACC or the American College of Cardiology.

the American College of Cardiology (Senior Associate Editor, Clinical

revascularization,

including

coronary

From the aDivision of Cardiology, New York University School of Medi-

Trials and News, ACC.org), Belvoir Publications (Editor-in-Chief, Harvard

cine, New York, New York; bInstitute for Medical Engineering and Sci-

Heart Letter), Duke Clinical Research Institute (clinical trial steering

ence, Massachusetts Institute of Technology, Cambridge, Massachusetts;

committees), Harvard Clinical Research Institute (clinical trial steering

and the cBrigham and Women’s Hospital Heart & Vascular Center, Har-

committee), HMP Communications (Editor-in-Chief, Journal of Invasive

vard Medical School, Boston, Massachusetts. Dr. Bangalore has served on

Cardiology), Journal of the American College of Cardiology (Guest Editor;

the Advisory Board for Abbott Vascular, Daiichi-Sankyo, The Medicines

Associate Editor), Population Health Research Institute (clinical trial

Company, and Pfizer; has received research grants from Abbott Vascular

steering committee), Slack Publications (Chief Medical Editor, Cardiology

and the National Heart, Lung, and Blood Institute; and has received

Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/

honoraria from Abbott Vascular, Daiichi-Sankyo, Merck, Abbott, Pfizer,

Treasurer), and WebMD (CME steering committees); has relationships

Boehringer Ingelheim, and AstraZeneca. Dr. Edelman has served on the

with Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steer-

advisory board for MiCell; and has received research support from 3M,

ing Committee (Chair), VA CART Research and Publications Committee

Boston Scientific, Edwards, Maquet, Medtronic, and the National

(Chair); has received research funding from Amarin, Amgen, AstraZe-

Institutes of Health. Dr. Edelman is funded, in part, by a grant from the

neca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories,

National Institutes of Health (R01 GM 49039). Dr. Bhatt serves on the

Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi, the Medi-

advisory board for Cardax, Elsevier Practice Update Cardiology, Med-

cines Company; has received royalties from Elsevier (Editor, Cardiovas-

scape Cardiology, and Regado Biosciences; is on the Board of Directors of

cular Intervention: A Companion to Braunwald’s Heart Disease); has

the Boston VA Research Institute and the Society of Cardiovascular

served as Site Co-Investigator for Biotronik, Boston Scientific, St. Jude

Patient Care; is the Chair of the American Heart Association Quality

Medical (now Abbott); has served as a trustee of the American College of

Oversight Committee; has served on Data Monitoring Committees for the

Cardiology and has performed unfunded research for FlowCo, PLx

Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical

Pharma, and Takeda.

Bangalore et al.

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JACC VOL. 69, NO. 25, 2017 JUNE 27, 2017:3067–9

BVS: Disappearing Evidence?

relief compared with EES (7). Thus, recent trials and

Median Rate of Device Thrombosis (Per 100 Patient-Years)

F I G U R E 1 Rate of Device Thrombosis With Metallic Stents and BVS Scaffold

meta-analyses suggest that proof of noninferiority for 1.20

1.20

elusive, and that the promise of added benefit for

1.00 0.80

0.80

resorption has yet to be established. 0.72

A few hypotheses have been put forth for continued 0.58

0.60

0.50

optimism

0.45

despite

the

current

sobering

results,

including the unexpected superior performance of the

0.33

0.40

comparator in clinical trials and an as yet inade-

0.20 0.00

efficacy and safety outcomes with the BVS compared with EES during the resorption phase remains

quately optimized BVS implantation procedure. In a sense, we may be stuck where we were when stents PES

BMS

SES

ZES

ZES-R

EES

BVS

were introduced: fairly certain that the new technology (bare-metal stents first and then DES later) is

Rates of device thrombosis among various metallic stents (adapted from the

superior to the predicate (balloon angioplasty first

meta-analysis by Bangalore et al. [1]) and the BVS scaffold (Abbott Vascular, Santa Clara,

and then bare-metal stents), but unable to demon-

California) (adapted from the meta-analysis of Sorrentino et al. [4]). BMS ¼ bare-metal

strate benefit without changing the domain space in

stents; BVS ¼ bioresorbable vascular scaffold; EES ¼ everolimus-eluting stents; PES ¼ paclitaxel-eluting stents; SES ¼ sirolimus-eluting stents; ZES ¼ zotarolimus-eluting stents; ZES-R ¼ zotarolimus-eluting stent-Resolute.

which comparisons are made or how the devices are designed or used. Alternatively, we may be where we were when brachytherapy was being celebrated: certain of the basic concepts at hand, but incapable of providing a coherent argument for logistical superi-

(up to 3 years) and show superiority (for clinical outcomes or preservation of revascularization options)

ority against an established, working intervention. We must then learn from our legacy and allow time-tested methods to declare how we should

after resorption (3). SEE PAGE 3055

consider this new technology. It is therefore time to increase our sophisticated clinical trials and spur

In this issue of the Journal, another meta-analysis

greater investment in nonclinical studies and design

raises safety concerns with this BVS, with a signifi-

refinement such that we allow a potential promise to

cant increase in the risk of target lesion failure (driven

play out before being accepted without question or

by a significant increase in target vessel myocardial

rejected prematurely. If the less than expected results

infarction and ischemia-driven target lesion revas-

with the BVS are due to better than expected perfor-

cularization) and scaffold thrombosis compared with

mance of the comparator (with very low stent

the everolimus-eluting stent (EES) at a median

thrombosis, better vasomotion, and greater angina

follow-up of 2 years (4). This meta-analysis includes

relief with EES than in prior studies), then time will

the very recent AIDA (Amsterdam Investigator-

tell. Furthermore, if scaffold thrombosis in the Absorb

Initiated Absorb Strategy All-Comers Trial) trial,

trials is in the range observed with first-generation

which published an early preliminary report on the

DES or bare-metal stents (Figure 1), and unaccept-

basis of their Data Safety Monitoring Board’s recom-

able in current-day practice because of unrefined

mendation and reported an almost 4-fold increase in

design or technique, then additional investigation is

the risk of scaffold thrombosis compared with an EES

required. Now is the time to ask if pre-dilation, sizing,

(5). Particularly concerning from recent trials and

post-dilation (PSP) can indeed normalize adverse

this meta-analysis is the increased risk of not only

events, as suggested in some post hoc analyses. The

early scaffold thrombosis, but also late and very late

ABSORB IV trial is one of the few large-scale trials in

(>1 year) scaffold thrombosis, with persisting concern

the PSP era, and early blinded, interim, pooled stent–

even at 3 years of follow-up, reminding physicians of

scaffold thrombosis data at 1 year show a very

similar concerns with first-generation DES (6). This is

competitive, low rate of 0.5%, which is encouraging

at a time when the guidelines have moved to

(8). However, in the AIDA trial, pre-dilation and

recommend a shorter minimal required duration of

post-dilation were performed in the majority of pa-

DAPT (6 months) with metallic DES in elective PCI,

tients (98.6% and 74%, respectively) in the BVS

and the concern for excessive very late stent throm-

group, yet the 2-year rate of definite or probable

bosis has largely dissipated with durable stents.

scaffold thrombosis remained unacceptably high, at

Moreover, in the ABSORB II trial, the BVS had neither

3.5% (5). Moreover, vessel size 2.25 mm or smaller,

superior vasomotion nor greater benefit in angina

inadequate device sizing, and lack of post-dilation

Bangalore et al.

JACC VOL. 69, NO. 25, 2017 JUNE 27, 2017:3067–9

BVS: Disappearing Evidence?

were not predictive of scaffold thrombosis in that

analysis and proceed to the second. The legacy of

trial, and the excess risk with the BVS seemed present

technology assessment and evaluation that has

in all patients studied in the AIDA trial (5). Thus, now

developed side by side with the evolution of

is the time to double down on investigation of what

remarkable cardiovascular interventional innovation

was appreciated relatively late in the DES era: that

over the last half-century provides us with a platform

stent dimensions, rather than material characteris-

to renew efforts to determine and define the limits of

tics, were dominant determinants of adverse effects.

emerging technology. New materials, designs, and

The first-generation BVS has a scaffold thickness of

implantation techniques must be considered, as it is a

150 m m, as thick as the Cypher stent (Cordis, Fremont,

community responsibility to learn as much as we can

California). Greater strut thickness increases the risk

before we bury a promise or accept a flawed early

of stent thrombosis (9) and it is therefore not sur-

incarnation of potential. In the meantime, let us hope

prising that the device, in general, would be more

that we do not repeat the history of the overly

thrombogenic than a comparator thin-strut DES.

exuberant early adoption of first-generation DES

Moreover, this stent becomes less forgiving in small

without understanding the greater stent thrombosis

vessels, with less than optimal deployment tech-

risk they posed compared with bare-metal stents,

niques, and perhaps with less than optimal adherence

with early reports having difficulty getting published,

and duration of DAPT.

and then initially being ignored (6) until the evidence

In summary, the well-done meta-analysis by

became overwhelming, which perhaps led to an

Sorrentino et al. (4) further elevates the safety

overreaction to the small, but real safety issue (6,10).

concerns with the first-generation BVS, and perhaps

Research on BVS should not stop—indeed, research

should kindle renewed research into revision of

should be redoubled. Thinner scaffolds, for example,

design and procedure. In the interim, it is prudent to

may greatly improve deliverability of the BVS and

apply the highest standards of appropriate patient

reduce scaffold thrombosis risks as well. However,

selection (vessel size $2.5 mm, compliance with

any newer BVS needs to undergo proper long-term

long-term DAPT for at least 3 years), and appropriate

evaluation in randomized trials versus the best

deployment techniques (including PSP). Still, hospi-

second-generation DES before clinical adoption.

tals, physicians, and patients should carefully weigh whether

the

increased

procedural

duration,

ADDRESS

FOR

CORRESPONDENCE:

Cardiac

Catheterization

Dr.

Sripal

complexity, and cost of the BVS, with likely a need for

Bangalore,

prolonged DAPT, are worth the theoretical, though

Cardiovascular

appealing, long-term potential of a coronary artery

Clinical Research Center, New York University School

returning to its native state. Perhaps this meta-

of Medicine, 550 First Avenue, New York, New

analysis is also a call to end the first phase of

York 10016. E-mail: [email protected].

Outcomes

Group,

Laboratory,

Cardiovascular

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everolimus-eluting metallic stents. J Am Coll Cardiol 2017;69:3055–66. 5. Wykrzykowska JJ, Kraak RP, Hofma SH, et al., AIDA Investigators. Bioresorbable scaffolds versus metallic stents in routine PCI. N Engl J Med 2017 Mar 29 [E-pub ahead of print]. 6. Bavry

AA,

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TJ,

Borek PP, Mood GR, Bhatt DL. Late thrombosis of drug-eluting stents: a meta-analysis of randomized clinical trials. Am J Med 2006;119: 1056–61. 7. Serruys PW, Chevalier B, Sotomi Y, et al. Comparison of an everolimus-eluting bioresorbable scaffold with an everolimus-eluting metallic stent for the treatment of coronary artery stenosis (ABSORB II): a 3 year, randomised, controlled, single-blind, multicentre clinical trial. Lancet 2016;388:2479–91.

8. Ellis SG. Everolimus-eluting bioresorbable vascular scaffolds in patients with coronary artery disease: ABSORB III trial 2-year results. Paper presented at: ACC 2017; March 18, 2017; Washington, DC. 9. Kolandaivelu K, Swaminathan R, Gibson WJ, et al. Stent thrombogenicity early in high-risk interventional settings is driven by stent design and deployment and protected by polymer-drug coatings. Circulation 2011;123:1400–9. 10. Bangalore S, Gupta N, Guo Y, Feit F. Trend in the use of drug eluting stents in the United States: insight from over 8.1 million coronary interventions. Int J Cardiol 2014;175:108–19.

KEY WORDS drug-eluting stents, myocardial infarction, percutaneous coronary intervention, thrombosis

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